A new drug target for Batten disease

Nature Neuroscience

September 23, 2013

An antioxidant drug that alleviates cell death and extends lifespan in a mouse model of Batten disease-a devastating childhood neurodegenerative disorder-is reported online this week in Nature Neuroscience. These results indicate that drugs with similar properties can potentially be used to treat the disease, as well as other diseases caused by comparable deficiencies.

Infantile neuronal ceroid-lipofuscinosis (INCL), a severe form of Batten disease, is a neurodegenerative disease that develops early in childhood and causes blindness, loss of motor and mental function, and eventually leads to death. It is caused by mutations in the PPT1 gene, leading to dysfunctional lysosome organelles, which are important for breaking down cellular waste material.These mutations prevent the degradation of certain proteins by a lysosomal enzyme, and the resultant accumulation of these proteins in cells is toxic.

Anil Mukherjee and colleagues find that a known chemical drug, NtBuHA, can compensate for the molecular defect caused by PPT1 mutations in a lab setting. This antioxidant drug is non-toxic and alleviated the abnormal accumulation of proteins and consequent death found in cultured cells taken from patients with INCL. In mice carrying a PPT1 mutation, NtBuHA prevented neuronal cell loss, mitigated behavioral deterioration and increased survival rates. Critically, NtBuHA also crossed the blood-brain-barrier, making it a promising therapeutic tool for central nervous system aspects of INCL.